CATH Classification

Domain Context

CATH Clusters

Superfamily Phosphorylase Kinase; domain 1
Functional Family Mitogen-activated protein kinase kinase kinase

Enzyme Information

2.7.11.25
Mitogen-activated protein kinase kinase kinase.
based on mapping to UniProt Q5TCX8
ATP + a protein = ADP + a phosphoprotein.
-!- This enzyme phosphorylates and activates its downstream protein kinase, EC 2.7.12.2, but requires MAPKKKK for activation. -!- Some members of this family can be activated by p21-activated kinases (PAK/STE20) or Ras. -!- While c-Raf and c-Mos activate the classical MAPK/ERK pathway, MEKK1 and MEKK2 preferentially activate the c-Jun N-terminal protein kinase(JNK)/stress-activated protein kinase (SAPK) pathway. -!- Mitogen-activated protein kinase (MAPK) signal transduction pathways are among the most widespread mechanisms of cellular regulation. -!- Mammalian MAPK pathways can be recruited by a wide variety of stimuli including hormones (e.g. insulin and growth hormone), mitogens (e.g. epidermal growth factor and platelet-derived growth factor), vasoactive peptides (e.g. angiotensin-II and endothelin), inflammatory cytokines of the tumor necrosis factor (TNF) family and environmental stresses such as osmotic shock, ionizing radiation and ischemeic injury. -!- Formerly EC 2.7.1.37.

UniProtKB Entries (1)

Q5TCX8
M3K21_HUMAN
Homo sapiens
Mitogen-activated protein kinase kinase kinase 21

PDB Structure

PDB 4UYA
External Links
Method X-RAY DIFFRACTION
Organism
Primary Citation
Recurrent Mlk4 Loss-of-Function Mutations Suppress Jnk Signaling to Promote Colon Tumorigenesis.
Marusiak, A.A., Stephenson, N.L., Baik, H., Trotter, E.W., Li, Y., Blyth, K., Mason, S., Chapman, P., Puto, L.A., Read, J.A., Brassington, C., Pollard, H.K., Phillips, C., Green, I., Overman, R., Collier, M., Testoni, E., Miller, C., Hunter, T., Sansom, O.J., Brognard, J.
Cancer Res.